• This month's issue features polyamines in milk, dairy’s association with improved short-term memory, reducing methane emission from livestock, and how lactation changes mammary fat cells. Gut Check: Polyamines in Human Milk Are Essential for Intestinal Maturation • Polyamines are amino acid-derived molecules found in all living cells and the milk of all mammals, including humans. • Human milk polyamine concentration is highest during the first weeks of lactation and varies across mothers. • Milk polyamines are essential for optimal maturation of the neonatal gut. Putrescine, spermine, and spermidine may not have the most appetizing names, but these amino acid-derived molecules (called polyamines) are ingredients of all mammal milks. The presence of polyamines in milk is not surprising—putrescine, spermine, and spermidine are manufactured by all mammalian body cells, including mammary tissue. But polyamines are not accidental milk ingredients, passed on simply because they are ubiquitous in mammalian cells. Research from human and non-human animal models demonstrates that optimal nutrient absorption, the composition of the intestinal microbiome, and even food allergy may all depend on a sufficient supply of polyamines during the neonatal period [1–11]. Milk polyamines, although odd in name, are essential for the proper maturation of the gastrointestinal tract in humans and other mammals. Making Polyamines Amino acids, the building blocks of proteins, are comprised of a carboxyl group and an amine group. Polyamines, as the name suggests, are composed of two or more amine groups. All living cells synthesize polyamines, and mammalian cells make three— putrescine, spermidine, and spermine—by removing the carboxyl groups from the amino acids methionine and ornithine [1]. In mammals, polyamines are involved in numerous functions within cells: they influence cellular growth, cellular differentiation, and the function of cell membranes, and also play a role in protein synthesis by regulating DNA and messenger RNA [1, 2]. Although all cells in a mammal’s body can synthesize polyamines, the importance of a sufficient dietary supply to maintain essential physiological functions indicates that cellular polyamine requirements exceed the body’s manufacturing capabilities [5, 7]. In this sense, polyamines are considered essential nutrients, just like certain amino acids, vitamins, and fatty acids [8]. The body’s polyamine requirements vary over time and are at their highest during growth periods, like infancy, which is characterized by rapid and widespread cellular proliferation [2]. Thus, the infancy period is a time when a sufficient dietary supply of polyamines may be especially critical. Polyamines are present in all mammalian milks, and although the concentration varies across species (e.g., human milk has higher values than cow milk), all milks peak in polyamine concentration during early lactation [1, 2]. For example, in human milk, polyamines increase in concentration during the first two weeks of lactation, reach their maximum value during the first month, and then decrease [1]. These changes in concentration are believed to be due to the action of the lactation hormone prolactin, which augments mammary gland synthesis of polyamines [2,8]. That milk from cows, rats, pigs, and humans all peak in polyamine concentration at the same stage of lactation indicates an important functional role for these molecules during this period. But if it were simply about growth (making new cells), polyamines would be important throughout lactation. Why are polyamines so important for newborn mammals? A Gut Feeling Mammals vary in developmental maturity at birth; some are born altricial requiring significant parental investment, whereas others are more developmentally mature, or precocial. One thing they all have in common, however, is the consumption of milk as a first food. During the neonatal period, the mammalian gastrointestinal tract undergoes rapid maturation in preparation for the introduction of non-milk foods. Polyamine ingestion from milk is believed to have an essential role in this accelerated development SPLASH! ® milk science update May 2017 Issue
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•
This month's issue features polyamines in milk, dairy’s association with improved short-term memory, reducing methane emission from livestock, and how lactation changes mammary fat cells. GutCheck:PolyaminesinHumanMilkAreEssentialforIntestinalMaturation
• Polyaminesareaminoacid-derivedmoleculesfoundinalllivingcellsandthemilkofallmammals,includinghumans.• Humanmilkpolyamineconcentrationishighestduringthefirstweeksoflactationandvariesacrossmothers.• Milkpolyaminesareessentialforoptimalmaturationoftheneonatalgut.
Putrescine,spermine,andspermidinemaynothavethemostappetizingnames,buttheseaminoacid-derivedmolecules(calledpolyamines)areingredientsofallmammalmilks.Thepresenceofpolyaminesinmilkisnotsurprising—putrescine,spermine,andspermidinearemanufacturedbyallmammalianbodycells,includingmammarytissue.Butpolyaminesarenotaccidentalmilkingredients,passedonsimplybecausetheyareubiquitousinmammaliancells.Researchfromhumanandnon-humananimalmodelsdemonstratesthatoptimalnutrientabsorption,thecompositionoftheintestinalmicrobiome,andevenfoodallergymayalldependonasufficientsupplyofpolyaminesduringtheneonatalperiod[1–11].Milkpolyamines,althoughoddinname,areessentialforthepropermaturationofthegastrointestinaltractinhumansandothermammals.
MakingPolyamines
Aminoacids,thebuildingblocksofproteins,arecomprisedofacarboxylgroupandanaminegroup.Polyamines,asthenamesuggests,arecomposedoftwoormoreaminegroups.Alllivingcellssynthesizepolyamines,andmammaliancellsmakethree—putrescine,spermidine,andspermine—byremovingthecarboxylgroupsfromtheaminoacidsmethionineandornithine[1].
Inmammals,polyaminesareinvolvedinnumerousfunctionswithincells:theyinfluencecellulargrowth,cellulardifferentiation,andthefunctionofcellmembranes,andalsoplayaroleinproteinsynthesisbyregulatingDNAandmessengerRNA[1,2].Althoughallcellsinamammal’sbodycansynthesizepolyamines,
theimportanceofasufficientdietarysupplytomaintainessentialphysiologicalfunctionsindicatesthatcellularpolyaminerequirementsexceedthebody’smanufacturingcapabilities[5,7].Inthissense,polyaminesareconsideredessentialnutrients,justlikecertainaminoacids,vitamins,andfattyacids[8].Thebody’spolyaminerequirementsvaryovertimeandareattheirhighestduringgrowthperiods,likeinfancy,whichischaracterizedbyrapidandwidespreadcellularproliferation[2].Thus,theinfancyperiodisatimewhenasufficientdietarysupplyofpolyaminesmaybeespeciallycritical.Polyaminesarepresentinallmammalianmilks,andalthoughtheconcentrationvariesacrossspecies(e.g.,humanmilkhashighervaluesthancowmilk),allmilkspeakinpolyamineconcentrationduringearlylactation[1,2].Forexample,inhumanmilk,polyaminesincreaseinconcentrationduringthefirsttwoweeksoflactation,reachtheirmaximumvalueduringthefirstmonth,andthendecrease[1].Thesechangesinconcentrationarebelievedtobeduetotheactionofthelactationhormoneprolactin,whichaugmentsmammaryglandsynthesisofpolyamines[2,8].Thatmilkfromcows,rats,pigs,andhumansallpeakinpolyamineconcentrationatthesamestageoflactationindicatesanimportantfunctionalroleforthesemoleculesduringthisperiod.Butifitweresimplyaboutgrowth(makingnewcells),polyamineswouldbeimportantthroughoutlactation.Whyarepolyaminessoimportantfornewbornmammals?
AGutFeeling
Mammalsvaryindevelopmentalmaturityatbirth;somearebornaltricialrequiringsignificantparentalinvestment,whereasothersaremoredevelopmentallymature,orprecocial.Onethingtheyallhaveincommon,however,istheconsumptionofmilkasafirstfood.Duringtheneonatalperiod,themammaliangastrointestinaltractundergoesrapidmaturationinpreparationfortheintroductionofnon-milkfoods.Polyamineingestionfrommilkisbelievedtohaveanessentialroleinthisaccelerateddevelopment
SPLASH!® milkscienceupdateMay2017Issue
ofthesmallandlargeintestines.Tounderstandandidentifyspecificfunctionsofpolyaminesinmammalianinfants,scientistsperformedexperimentsonnon-humananimalsthatincludedstudygroupsthatdidnotreceiveanypolyamines—whatbetterwaytofigureoutwhatsomethingdoesthantoobservewhathappenswhenyoutakeitaway.Theearlieststudies(duringthe1990s)focusedonratmodelsandfoundthatratpupsreceivingformulasupplementedwithpolyamines(specificallyspermineandspermidine)hadseveralphysiologicaldifferencesrelatingtogutmaturationcomparedwithcontrolsthatconsumedfewerornopolyamines.Keydifferencesincludedheightenedenzymaticactivityofthegut(includingenzymesresponsibleforproteindigestion)anddecreasedgutpermeabilitytomacromolecules[reviewedin5].Takentogether,theseobservationsledDandrifosseandcolleagues[5]toproposethatpolyaminesplayaroleinthedevelopmentoffoodallergy.Becausefoodproteinsarethesourceoffoodallergies,improvedproteindigestion(viaincreasedprotein-digestingenzymeactivity)coupledwithalesspermeablegut,reducesthepotentialforfoodantigenstomaketheirwayintothebloodstreamandtocomeincontactwiththeimmunesystem.Infantswithmorepermeablegutsduetoreducedpolyamineintake(particularlyspermine)wouldthusbeatahigherriskfordevelopingfoodallergies[5].Dandrifosseandcolleaguestestedtheirhypothesisinasmallsample(n=45)ofhumansubjects.First,milksampleswerecollectedfrommothersandanalyzedforpolyamineconcentration.Fiveyearslater,allmotherswerecontactedandsentaquestionnairerequestinginformationaboutenvironmentalandfoodallergiesintheirchild.Theyfoundthatbreastfedchildrenwithanallergyatage5consumedmilkwithlowerpolyamineconcentrationthanthosewithoutallergies.Theyevenestablishedwhattheybelievedwasa“criticalvalue”belowwhichchildrenhaveanincreasedriskofallergy(5.02nmol/ml)[5].Researchershavelonggrappledwiththequestionofwhetherbreastfeedingisprotectiveagainstallergy.Whereasseveralstudieshavefounddecreasedriskassociatedwithbreastfeeding,manyhavefoundtheriskfactorsareidenticalbetweentheformula-andbreastfedinfants.Thisstudy[5]helpstomakesenseofthosecontradictoryfindingsbyhighlightingthedifferencesinriskassociatedwithbreastfeedingalone.Somemothersproducemilkwithrelativelyhighconcentrationsofspermineandspermidinewithlittletonoriskofproducingallergy,whereasothersproducemilkwithlowerconcentrationsmoresimilartothosefoundinformula,whichhasaprobabilityofproducingafoodallergythatisbelievedtobecloserto80%[2,5].Infantformulaismadefromsoyorcowmilk,whichcanexplainthelowerconcentrationofpolyaminescomparedwithbreastmilk[9].Butwhatcanexplainthevariationinbreastmilkpolyamineconcentrationamonghumanmothers?Severallinesofevidencesuggestthatthepolyaminecompositionofthematernaldietinfluencesmilkpolyamineconcentration.Citrusfruits,suchasorangesandgrapefruitarehighinputrescine,whereasbeansandmeataregoodsourcesofspermineandspermidine[8].However,polyaminesarefoundinsomanydifferenttypesoffoodsthatitisdifficulttodetermineaparticulardietarypatternthatmayresultinhigherpolyamineintake.Gómez-Gallagoetal.[4]foundsignificantdifferencesintheconcentrationofmilkputrescineandspermidine(butnotspermine)acrossfourdifferenthumanpopulations(Finland,Spain,China,andSouthAfrica),whichtheyattributedtodietarydifferencesacrosscultures.AtiyaAlietal.demonstratedthisrelationshipwithamoredetailedstudy[7],whereinbreastfeedingmothersofnewbornskepta3-dayfooddiary.Aftercalculatingdailyintakeofallthreepolyamines,theyfoundthattheconcentrationofputrescine,spermidine,andspermineinmilkwereallsignificantlyassociatedwiththeirconcentrationinthediet.Inanotherstudy,AtiyaAlietal.[8]foundthatobesemothersproducedsignificantlylowerlevels(14%)ofputrescineandspermidine(butagain,notspermine)comparedwithmotherswithahealthybodymassindex.Althoughobesityitselfcouldbeacontributingfactortomilkpolyaminelevels,theyobservedthatobesemothersthatreceivednutritionalcounselingandadviceduringthestudyperiodincreasedtheirmilkpolyaminelevelstothosematchinghealthycontrols.Thisfindingsuggestsitisnotwhatthemotherhaseateninthepast,butwhatthemotheriscurrentlyconsumingthatdeterminesmilkpolyamineconcentration.Except,perhaps,forspermine,theverypolyamineimplicatedingutpermeability.Allthreestudies[4,7,8]concludedthatspermineappearslesssusceptibletoenvironmentalinfluences.However,interpretationsofresultsarecomplicatedbythefactthatpolyaminescanbeinterconvertedbytheinfant(putrescineisaprecursortospermineandspermidine,andcanbebrokendowntomakeeitherpolyamine;spermineandspermidinecanalsobeconvertedbackintoputrescine).Thus,thetotalcontentofpolyaminesinmilkshouldbethemetricofinterest.
GrowingtheGut
Tworecentanimalstudieshaveprovidedmoredetailedevidenceofthepotentialhealthoutcomesassociatedwithlowmilkpolyamineconcentration[6,10].VanWettereetal.[10]wereinterestedintherelationshipbetweenmilkpolyaminesandthedevelopmentoftheabsorptive,ormucosal,surfaceoftheintestines(thatis,thesurfacewherethefoodmeetstheintestinalcells).Themucosalsurfaceoftheintestineslooksabitlikearollercoaster,withaseriesofpeaks(calledvilli)andvalleys(calledcrypts).Itisalongthissurfacethatnutrients(includingproteins,fats,carbohydrates,vitaminsandminerals)areabsorbedintotheintestinesforeventualtransferintothebloodstream.Thisrollercoaster-likestructureisaratheringeniouswayofgettingmoresurfaceareafornutrientabsorption;thehigherthepeaksandthedeeperthevalleys,themorecellsforfoodtocontactforabsorption.VanWettereetal.[10]foundthatpigletssupplementedwithspermineeveryotherdayovera10-dayperiodhadanincreaseinthesurfacearea
oftheirgastrointestinaltract.Andtheincreasewassignificant;sperminesupplementationwasassociatedwitha41%increaseinvillusheight(thepeaks)anda21%decreaseincryptdepth(thevalleys)alongthesmallintestine[10].Importantly,theinvestigatorswereabletolinkthechangesintheintestinalsurfaceareawithimprovedgrowthbothduringsupplementationandafterweaning[10].Higherhillsandlowervalleysmeantimprovednutrientabsorption,whichtheyarguewascriticalinhelpingthepigletsmaintainoptimalgrowthratesastheytransitionedfrommilktonon-milkfoods.Thesurfaceareaoftheintestinesisnottheonlythinginthegutthatmilkpolyamineshelptogrow—thesemoleculesarealsogrowthfactorsforthehealthybacteriathatpopulatethegastrointestinaltract.Inanewstudy,Gómez-Gallagoandcolleagues[6]foundthatnewbornmiceconsumingpolyamine-supplementedformulahadbacterialcommunitiessimilartothoseofmiceconsumingtheirmother’smilk,validatingtheirresultsfromapreviousstudy[11].Becauseofthestrongconnectionbetweenthedevelopmentofahealthygutmicrobiomeandimmunefunction,theirnewstudywentonestepfurtherandinvestigatedthetypesoflymphocytes(cellsoftheimmunesystem)thatpopulatedthegutaswellasgenesrelatedtoimmuneactivitywithinthegut.Again,micefedthesupplementedformulaweregroupedstatisticallyclosertothesucklingmicethanthoseconsumingformulawithoutpolyamines[6].Itisintriguingtothinkthathumaninfantswouldhaveidenticalresponsestopolyaminesupplementationasthepigletsandmousepupsintheexperimentalmodels.Optimalintakelevelsofpolyaminesforhumaninfantshavenotbeenestablished.However,bothstudies[6,10]foundsignificantresultsusingconcentrationsofpolyaminesthatwerelowerthanthoseinmouseorpigmilk,indicatingthathumanbreastmilkconcentrationscouldbeahelpfulsignpostfordetermininganappropriateconcentration.Couldsomethingassimpleaspolyaminesupplementationinformula(orincreasedpolyamineconsumptioninthedietofbreastfeedingmothers)helpresolvehealthissuesassociatedwithfoodallergy,nutrientabsorption,ortheintestinalmicrobiome?Gómez-Gallagoetal.[6]suggestthisquestionisimportantenoughtogo“onestepforward”byreproducingtheirexperimentsusinghumansubjects.
Löser,C.,2000.Polyaminesinhumanandanimalmilk.BritishJournalofNutrition,84(S1):55-58. Larqué,E.,Sabater-Molina,M.,Zamora,S.,2007.Biologicalsignificanceofdietarypolyamines.Nutrition,23(1):87-95. Plaza-Zamora,J.,Sabater-Molina,M.,Rodriguez-Palmero,M.,Rivero,M.,Bosch,V.,Nadal,J.M.,Zamora,S.,Larque,E.,2013.Polyaminesinhumanbreastmilkfor
pretermandterminfants.BritishJournalofNutrition,110(03):524-528. Gómez-GallegoC,KumarH,García-MantranaI,duToitE,SuomelaJP,LinderborgKM,ZhangY,IsolauriE,YangB,SalminenS,ColladoMC.,2017.Breastmilk
polyaminesandmicrobiotainteractions:Impactofmodeofdeliveryandgeographicallocation.AnnalsofNutritionandMetabolism,March17. Dandrifosse,G.,Peulen,O.,ElKhefif,N.,Deloyer,P.,Dandrifosse,A.C.Grandfils,C.,2000.Aremilkpolyaminespreventiveagentsagainstfoodallergy?.
ProceedingsoftheNutritionSociety,59(01):81-86. Gómez-GallegoC.,GarciaRomoM.,FriasR.,Periago,M.J.,Ros,G.,SalminenS.,ColladoM.C.,2017.Miceexposedtoinfantformulaenrichedwithpolyamines:
impactonhosttranscriptomeandmicrobiome.Food&Function. AtiyaAli,M.,Strandvik,B.,Sabel,K.G.,PalmeKilander,C.,Strömberg,R.Yngve,A.,2014.Polyaminelevelsinbreastmilkareassociatedwithmothers’dietary
intakeandarehigherinpretermthanfull-termhumanmilkandformulas.JournalofHumanNutritionandDietetics,27(5):459-467. AtiyaAli,M.,B.Strandvik,C.Palme-Kilander,A.Yngve.,2013.Lowerpolyaminelevelsinbreastmilkofobesemotherscomparedtomotherswithnormalbody
weight.JournalofHumanNutritionandDietetics26(s1):164-170. Buts,J.P.,DeKeyser,N.,DeRaedemaeker,L.,Collette,E.,&Sokal,E.M.,1995.Polyamineprofilesinhumanmilk,infantartificialformulas,andsemi-elemental
diets.Journalofpediatricgastroenterologyandnutrition,21(1):44-49. vanWettere,W.H.E.J.,Willson,N.L.,Pain,S.J.,Forder,R.E.A.,2016.Effectoforalpolyaminesupplementationpre-weaningonpigletgrowthandintestinalcharacteristics.animal(Oct1):.1-5.
Gómez-GallegoC.,Collado,M.C.,Perez,G.,Ilo,T.,Jaakkola,U.M.,Bernal,M.J.,Periago,M.J.,Frias,R.,Ros,G.,Salminen,S.,2014.Resemblingbreastmilk:influenceofpolyamine-supplementedformulaonneonatalBALB/cOlaHsdmousemicrobiota.BrJNutr111:1050-1058.
ContributedbyDr.LaurenMilliganNewmarkResearchAssociateSmithsonianInstitute
HighDairyConsumptionisAssociatedwithBetterShort-TermMemoryinMen• Anewstudyinvestigatestheeffectsofdairyintakeonshort-termmemory,usingmatchedpairsoftwinstoadjustfor
geneticandfamilyenvironmentalfactors.• Thestudyfoundthathigherdairyproductconsumptionwassignificantlyassociatedwithbettershort-termmemoryin
menbutnotwomen.• Short-termmemoryassessmentcanbeusedtoscreenformildcognitiveimpairmentandAlzheimer’sdisease,andthe
newstudythussuggeststhatdairyintakecouldpotentiallyreducecognitivedeclineinmenindependentofgeneticsandfamilyenvironment.
Eatingdairyproductspositivelyinfluencesbrainfunction,withhigherdairyintakeassociatedwithimprovedcognitiveabilityandshort-termmemory,andreducedcognitivedeclineanddementia[1-8].However,previousstudiesthatlookedattheseassociationscouldnotruleouttheeffectsofconfoundingfactorssuchasgeneticsandfamilyenvironment,whicharealsoknowntoaffectcognitiveabilityandfoodintake[9,10].
Onewaytoteaseaparttheeffectsofdairyfromthoseofgeneticsandfamilyenvironmentwouldbetostudypairsoftwins,andthat’sexactlytheapproachtakenbySoshiroOgataandhiscolleaguesatOsakaUniversityGraduateSchoolofMedicine.Inanewstudy,theresearchersinvestigatedtheassociationbetweendairyproductintakeandshort-termmemory,usingnaturallymatchedtwinpairstoadjustfornearlyallgeneticandfamilyenvironmentalfactors[11].
OgataandhiscolleaguescollecteddatafromtheOsakaUniversityCenterforTwinResearch,andanalyzed39Japanesemaletwinpairsand139Japanesefemaletwinpairs[11].Toassessshort-termmemory,theresearchersaskedparticipantstolistentotwoshortstoriesandimmediatelyrecallthedetails.Theresearchersassessedparticipants’dietsusingaself-administereddiethistoryquestionnaire,andtheparticipants’dairysourcesconsistedoflow-fatandfull-fatmilkandyogurt.Theresearchersfoundthathigherconsumptionofdairyproductswassignificantlyassociatedwithbettershort-termmemoryinmen,evenafteradjustingfornumerousconfoundingfactorsincludingalmostallgeneticandfamilyenvironmentalfactors.Theresearchersdidnotfindasimilarassociationinwomen.
Short-termmemoryassessmentcanbeusedtoscreenformildcognitiveimpairmentandAlzheimer’sdisease[13].TheresultsofOgataetal.[12]thussuggestthateatingmoredairyproductscouldpotentiallyreducecognitivedeclineinmenindependentofgeneticsandfamilyenvironment.It’sunclearfromthisstudywhyhigherdairyintakewasassociatedwithbettershort-termmemoryinmenandnotinwomen.Theresultsareconsistentwithapreviouslongitudinalstudythatfoundnosignificantassociationbetweencognitivefunctionandconsumptionofdairyproductsinwomen[14].Theresearchersalsosuggestthatthesexdifferencesintheeffectsofdairyonshort-termmemorymightbeduetodifferencesintheagedistributionofmenandwomeninthestudy,orduetopreviouslydescribedseasonalvariationsindairyconsumptioninJapanesewomenbutnotmen[15].Futurestudiesareneededtoelucidateboththereasonsfortheobservedsexdifferencesandthemechanismsbywhichdairyconsumptionaffectscognitivefunction.Onepotentialmechanisminvolvestheeffectsofincreaseddairyproductconsumptiononareducedriskofdevelopingtype2diabetesandhypertension,whicharepotentialriskfactorsforcognitivedecline[16-18].DairyalsocontainsnutritionalcomponentssuchascalciumandvitaminB12thatareknowntohavesomecognitiveeffects.Theauthorssuggestthatfollow-upstudiescouldmeasuretheeffectsofdairyonothercognitiveabilitiesinadditiontoshort-termmemory.Thesestudiescouldalsoinvestigatedifferencesbetweentheeffectsoffull-fatandlow-fatdairyproductsoncognitivefunction,aspreviousstudiesindicateddifferencesintheireffects[19,20].Byshowingthatdairymayinfluenceshort-termmemoryregardlessofgeneticandenvironmentalfactors,thecurrentstudyindicatesthatlookingmoredeeplyattheeffectsofdairyoncognitionisano-brainer.
Gomez-PinillaF.Brainfoods:theeffectsofnutrientsonbrainfunction.NatRevNeurosci.2008Jul;9(7):568-78. EverittA.V.,HilmerS.N.,Brand-MillerJ.C.,JamiesonH.A.,TruswellA.S.,SharmaA.P.,MasonR.S.,MorrisB.J.,LeCouteurD.G.Dietaryapproachesthatdelayage-
relateddiseases.ClinIntervAging.2006;1(1):11-31. CamfieldD.A.,OwenL.,ScholeyA.B.,PipingasA.,StoughC.Dairyconstituentsandneurocognitivehealthinaging.BrJNutr.2011Jul;106(2):159-74. RahmanA.,SawyerBakerP.,AllmanR.M.,ZamriniE.Dietaryfactorsandcognitiveimpairmentincommunity-dwellingelderly.JNutrHealthAging.2007Jan-
Feb;11(1):49-54. ParkK.M.,FulgoniV.L.TheassociationbetweendairyproductconsumptionandcognitivefunctionintheNationalHealthandNutritionExaminationSurvey.BrJ
Nutr.2013Mar28;109(6):1135-42. CrichtonG.E.,EliasM.F.,DoreG.A.,RobbinsM.A.Relationbetweendairyfoodintakeandcognitivefunction:theMaine-SyracuselongitudinalStudy.IntDairyJ.
2012Jan1;22(1):15-23. YamadaM.,KasagiF.,SasakiH.,MasunariN.,MimoriY.,SuzukiG.Associationbetweendementiaandmidliferiskfactors:theradiationeffectsresearch
foundationadulthealthstudy.JAmGeriatrSoc.2003Mar;51(3):410-4. OzawaM.,OharaT.,NinomiyaT.,HataJ.,YoshidaD.,MukaiN.,NagataM.,UchidaK.,ShirotaT.,KitazonoT.,KiyoharaY.Milkanddairyconsumptionandriskof
dementiainanelderlyJapanesepopulation:theHisayamaStudy.JAmGeriatrSoc.2014Jul;62(7):1224-30. LeeT.,HenryJ.D.,TrollorJ.N.,SachdevP.S.Geneticinfluencesoncognitivefunctionsintheelderly:aselectivereviewoftwinstudies.BrainResRev.2010
Sep;64(1):1-13 HasselbalchA.L.,HeitmannB.L.,KyvikK.O.,SørensenT.I.Studiesoftwinsindicatethatgeneticsinfluencedietaryintake.JNutr.2008Dec;138(12):2406-12. OgataS.,TanakaH.,OmuraK.,HondaC.;OsakaTwinResearchGroup,HayakawaK.Associationbetweenintakeofdairyproductsandshort-termmemorywithandwithoutadjustmentforgeneticandfamilyenvironmentalfactors:Atwinstudy.ClinNutr.2016Apr;35(2):507-13.
HayakawaK.,IwataniY.AnoverviewofmultidisciplinaryresearchresourcesattheOsakaUniversityCenterforTwinResearch.TwinResHumGenet.2013Feb;16(1):217-20.
RabinL.A.,PareN.,SaykinA.J.,BrownM.J.,WishartH.A.,FlashmanL.A.,SantulliR.B.DifferentialmemorytestsensitivityfordiagnosingamnesticmildcognitiveimpairmentandpredictingconversiontoAlzheimer’sdisease.NeuropsycholDevCognBAgingNeuropsycholCogn.2009May;16(3):357-76.
VercambreM.N.,Boutron-RuaultM.C.,RitchieK.,Clavel-ChapelonF.,BerrC.Long-termassociationoffoodandnutrientintakeswithcognitiveandfunctionaldecline:a13-yearfollow-upstudyofelderlyFrenchwomen.BrJNutr.2009Aug;102(3):419-27.
SasakiS.,TakahashiT.,IitoiY.,IwaseY.,KobayashiM.,IshiharaJ.,AkabaneM.,Tsugane,S.;JPHC.Foodandnutrientintakesassessedwithdietaryrecordsforthevalidationstudyofaself-administeredfoodfrequencyquestionnaireinJPHCStudyCohortI.JEpidemiol.2003Jan;13(1Suppl):S23-50.
Soedamah-MuthuS.S.,VerberneL.D.M.,DingE.L.,EngberinkM.F.,GeleijnseJ.M.Dairyconsumptionandincidenceofhypertension:adose-responsemeta-analysisofprospectivecohortstudies.Hypertension.2012Nov;60(5):1131-7.
MonetteM.C.E.,BairdA.,JacksonD.L.Ameta-analysisofcognitivefunctioninginnondementedadultswithtype2diabetesmellitus.CanJDiabetes.2014Dec;38(6):401-8.
GiffordK.A.,BadaraccoM.,LiuD.,TripodisY.,GentileA.,LuZ.,PalmisanoJ.,JeffersonA.L.Bloodpressureandcognitionamongolderadults:ameta-analysis.ArchClinNeuropsychol.2013Nov;28(7):649-64.
CrichtonG.E.,MurphyK.J.,BryanJ.Dairyintakeandcognitivehealthinmiddle-agedSouthAustralians.AsiaPacJClinNutr.2010;19(2):161-71. AlmeidaO.P.,NormanP.,HankeyG.,JamrozikK.,FlickerL.Successfulmentalhealthaging:resultsfromalongitudinalstudyofolderAustralianmen.AmJGeriatrPsychiatry.2006Jan;14(1):27-35.
ContributedbyDr.SandeepRavindranFreelanceScienceWriterSandeepr.comLesseningtheGasLeak
• Methaneemissionsfromlivestock—intheformofbelchesandflatulence—composeanon-negligibleproportionofgreenhousegasemissions.
• Inanexperiment,theadditionofthemethaneinhibitor,3-nitrooxypropanol(3NOP),toanimalfeedcutdairycattle’smethaneemissionsbyabout30%,withoutaffectingtheanimals’productivity.
• Crucially,theexperimentwasconductedoveraprolongedperiodundersimilarconditionstohowdairycattlearenormallykeptonNorthAmericancommercialfarms.
Ateamofscientistsfromfourcontinentshasgatheredevidencetodemonstratethatitshouldbepossibletocutmethaneemissionsfromdairycattlewithoutreducinghowmuchmilktheyproducenorhavingtochangetheconditionsinwhichtheyarekept.Theanswerissimplytoaddaningredienttotheirfeed.Intestslastingseveralmonths,thisingredient,3-nitrooxypropanol,knownas3NOP,cutmethaneemissionsfromHolsteindairycowsbyabout30%[1].Achievingsuchareductioninentericmethaneoutputacrossthedairyindustrywouldbeasignificantcontributiontowidereffortstoreducegreenhousegasemissions.
Asruminants,dairycattlearehometobacteriathatfermenttheirfood,readyingitforregurgitationascudbeforeproperdigestiontakesplace.Methanegasisgeneratedduringthefermentationprocessandeventuallymakesitswayintotheatmospherefromeitheroneendofthecowortheother.Allofthismethane—emanatingfromcattleallovertheworld—isaprimetargetformitigatinggreenhousegasemissions,notleastbecausemethaneisafarmorepotentgreenhousegasthancarbondioxide.Althoughestimatesoflivestock’scontributiontoanthropogenicemissionsvary[2],itiswidelyacceptedthatemissionsfromcattledwarfthosefromotherkindsoflivestock[3].Theauthorsoftherecentstudysetouttoevaluatethereal-worldeffectivenessofacompoundthattheyknewhadthepotentialtocuthow
muchmethanetheaveragedairycowreleasesintotheatmosphere.3NOPwasfirstidentifiedbyacomputermodelinalaboratoryinBasel,Switzerland.Researcherstheresingleditoutforfurthertestingbecauseafteritwasfoundtobindtheactivesiteofamethane-producingenzymethatoccursinoneofthemostcommonkindsofruminantfermentationbacteria,Methanobrevibacterruminantium.Bybindingthisactivesite,3NOPstopstheenzymefromworkingandlimitsthebacterium’sgrowth(whilstleavingunaffectedthegrowthofnon-methane-producingbacteria)[4].Testingthereal-worldeffectivenessrequired48Holsteins.Thecowswererandomlyassignedtoeitheracontrolgroup,ortoagroupthatwouldcontinuallyreceivelow,medium,orhighamountsof3NOPinitsfood.Manyaspectsofthecows’milkproductionandhealthwerecloselymonitored,andalloftheirmethane,carbondioxideandhydrogenemissionsweremeasuredregularlythroughouttheexperiment.Importantly,theHolsteinswerekeptinconditionssimilartothoseoncommercialdairyfarmsandmonitoredforathreefullmonths—whichislongerthanmostmethane-inhibitortestsofthepast.Theextendedperiodoffersaninsightintowhetherseveralkeyconcernsareavoided,suchasifthecowseatlessovertimeintheconditionwherethecompoundisaddedtotheirfood;iftheirmilkproductiontailstailedoff;andifmethane-producingbacteriacanshifttheirmetabolicstrategyandadaptto3NOP.Ifthelatteroccurs,methaneproductionmaystarttoriseagainafteritdips—despitethecowscontinuingtogobble3NOPineverymeal.Afterthethreemonthswereup,theHolsteinsthatatethemost3NOPconsistentlyemittedtheleastmethane.Indeed,theygenerated32%lessmethanethancowsinthecontrolgroup,whichconsumedno3NOPbutanotherwiseidenticaldiet.Thetrendinthedatashowedlittlesignofabating,indicatingthatmethane-generatingbacteriadonotreadilyfindawayaroundthemethaneinhibitor’seffects.The3NOP-consumingcowsproducedmorehydrogen,whichwastobeexpectedifthefermentationprocesswas
interruptedasthescientistsforesaw(becausehydrogenisanintermediateinthisprocess).Carbondioxideemissionsdidnotvary,however,whateverexperimentalgroupthecowswerein.Thecows’othervitalstatisticswereencouraging.Eating3NOPdidnotcurbtheirappetites;instead,itseemstohavehelpedthemputonweight.Thisisprobablybecausethefoodenergynormallylostasmethanebecamemetabolicallyavailabletotheseanimals.Additionalenergyavailabilitymayalsoexplainthegreatermilkproteinandlactoseyieldsinthe3NOP-eatingcows’milk,sinceitcould,inpart,havebeenplowedintosynthesizingthesemilkconstituents.Overall,theconcentrationoffatinmilkwasunaffectedbyadietcontaining3NOP(eventhoughtherelativeabundancesofparticularfatsdidchange).Whilefurthertestingislikelyrequiredonlargerherdsanddifferentbreeds,3NOPdoesappeartogeneratethekindofmethanemitigationthatthedairyindustryisunderpressuretoachieve,withoutimpactinghowfarmersgoabouttheirbusiness.Thismattersinmanycountrieswheretheindustrycontributesasizeableportionoftotalgreenhousegasemissions,suchasNewZealand.ButitalsocomesatanauspicioustimeintheUnitedStatesbecausetheU.S.EnvironmentalProtectionAgency’sestimatesforentericmethaneemissionsoverthecountryhave,inthepastfewyears,comeunderfire.SatellitedatahavesuggestedthattheAgencyunderestimatestheseemissionsbyupto85%[2].3NOPcouldhelptoreducetheproblem.
HristovaA.N.,OhaJ.,GiallongoaF.,FrederickaT.W.,HarperaM.,WeeksaH.L.,BrancobA.F.,MoatecP.J.,DeightoncM.H.,WilliamscS.R.O.,KindermanndM.,DuvaleS.(2015)Aninhibitorpersistentlydecreasedentericmethaneemissionfromdairycowswithnonegativeeffectonmilkproduction.PNAS,112(34):10663–10668.
WechtK.J.,JacobD.J.,FrankenbergC.,JiangZ.,BlakeD.R.(2014)MappingofNorthAmericanmethaneemissionswithhighspatialresolutionbyinversionofSCIAMACHYsatellitedata.JGeophysResAtmos119(12):7741–7756.
HerreroM.,HendersonM.,HavlíkP.,ThorntonP.K.,ConantR.T.,SmithP.,WirseniusS.,HristovA.N.,GerberP.,GillM.,Butterbach-BahlK.,ValinH.,GarnettT.&StehfestE.(2016)Greenhousegasmitigationpotentialsinthelivestocksector.NatureClimateChange6:452-461.
DuinE.C.,WagnerT.,ShimaS.,PrakashD.,CroninB.,Yáñez-RuizD.R.,DuvalS.,RümbeliR.,StemmlerR.T.,ThauerR.K.,KindermannM.(2016)Modeofactionuncoveredforthespecificreductionofmethaneemissionsfromruminantsbythesmallmolecule3-nitrooxypropanol.PNAS113(22):6172-7.
ContributedbyAnnaPetherickProfessionalsciencewriter&editorwww.annapetherick.com
TheManyLivesofFatCells• Thereareatleastthreetypesoffatcells,eachwithdifferentfunctions.• Substantialchangesinmammaryfatcellsoccurduringthelactationcycle.• Somemilkproducingcellsinmammarytissuebecomebrown-likefatcellswhenmilkisnolongerproduced.
Peopleobsessaboutfat.Manyhavemuchmorefatthantheyneeddepositedinvariouslocationsinthebodyanditthreatensbothhealthandfashion.Fathasnowdevelopedabadreputation.Intimesgoneby,abitofextrafatmeantalifesavingenergyreserveintimesoffoodscarcity.Indeed,themetabolismwehaveinheritedfromourancestorswasoriginallyfine-tunedtosuitthefeastorfaminelifestyleofthepast;however,itisnotsuitableformostpeopleintoday’sworldwherefoodabundanceisthenorm.Fatisasimplething,orsowethought.Therehavebeenseveralsurprisesoflate.
FatTissuesAreNotAllTheSame
Thebodyofamammalcontainsdifferenttypesoffat,eachwithspecificfunctions.Scientistshavelongknownthatthemainfunctionsoffatinanimalsarethestorageofenergyintheformofspecificfattyacidscalledtriglyceridesandtheprotectionofinternalorgansfrombluntforcetrauma.Thefattypethatlargelycharacterizesthesefunctionsiswhitefat(adipose)tissue,whichisprimarilymadeoffatcellscalledwhiteadipocytesthatarerelativelylarge,andasinglelargeglobuleoffattypicallydominatestheirinternalstructure.Thisisthefatweallknowsowell.Asecondtypeoffat,brownadiposetissue,wasfirstdiscoveredinhibernatingmammals,likebears.Unlikewhiteadiposetissue,brownadiposetissuehastheuniquepropertyofheatgeneration,whichallowshibernatinganimalstowithstandseverecold.Thisadiposetissueconsistsofbrown
adipocyteswitheachcontainingmanysmallfatglobulesandalargenumberofmitochondria,thepowerhousesofacell.Thelattergivethistissueitsbrowncolor,andaspecificbiochemicalreactioninthemgeneratesheat.Newbornoffspringofnon-hibernatingmammals,includinghumans,alsocontainbrownadiposetissuethatprotectsthemfromthecoldwhentheyareattheirmost
vulnerable.Withinafewweeksofbirth,however,thebrownadiposetissueinmostnewbornmammalsislostandreplacedbywhiteadiposetissue[1].Oneofthescientificsurprisesdiscoveredoverthelastdecadeisthatadulthumanshaveasmallamountofbrownadiposetissueintheneckandshoulderregion(interscapularregion)closetothemajorbloodvesselsleadingtothebrain.Presumably,theprimaryfunctionofthisadiposetissueistoheatbloodflowingtothebrainwhenthebodyisexposedtoverycoldtemperatures.Thisadiposetissuemayalsohavearoleinregulatingmetabolism[1–3].Anothersurprisemadeonlyoverthelastfewyearswasthediscoverybyscientistsofathirdtypeoffatthatconsistsofbrown-likeadipocytesinducedbydietorcoldwithinwhiteadiposetissue[2,3].Researcherscallthistypeoffatbeigeadiposetissue.Eventhoughbeigeadipocyteslooklikebrownadipocytes,theyaredifferentintermsoftheircellularoriginandfunction.Scientistsfromseveralgroupshaveconcludedthatbeigeadiposetissuemighthelpprotectpeoplefromobesitybyincreasingtherateofmetabolismoffattyacids[3].Consequently,manyscientificgroupsinboththepublicdomainandprivatecompaniesareinvestigatingdietaryanddrug-basedstrategiesthatmayincreasetheamountofbeigeadiposetissueinobesepeople[3,4].
TheLactationCycleCausesSubstantialChangesinMammaryFatCells
AscientificgroupledbySaverioCintithatinvolvedresearchersfromsixuniversitiesandthreecontinentsrecentlyconcludedthatadipocytespresentinmammarytissueundergoadramaticchangeduringthelactationcycle[5].Thisisthecycleofmilkproductionandcessationoccurringinmammarytissuebetweenonepregnancyandthenext.Duringlactation,mammaryepithelialcellssecretethevariouscomponentsofmilkintomammarytissuealveoli(smallsacsfoundwithinthemammarygland).Whenthereisnolongeranysucklingbytheyoungandremovalofmilkfrommammarytissue,thetissueundergoesadramaticcellularrestructuringcalledinvolutionthatstopsmilkproduction.Somemammaryepithelialcellsdiebutmostreverttoaquietstatenolongerproducingmilk.Theresearchersusedtheremarkablegenetictoolsavailableforstudyingtransgenicmicetovisualizethefateoffatcellslyingadjacenttothemammaryepithelialcellsduringthelactationcycle.Theyusedlightmicroscopyandtheamazingpoweroftransmissionelectronmicroscopytoproduceexquisiteimagesoftheseadiposecellsduringandafterlactation.Thescientists’approachalloweddeterminationoftheadipocytetypeinmammarytissuethroughoutthelactationcycle.Cinti[1]showedthatduringpregnancyandlactationsomewhiteadipocytesinthemammaryglandconvertedintomilk-secretingepitheliacells,quitearemarkablecellulartransformation.Thiswasalreadyknown[6].Thesurprisewasthatwhentheyexaminedmammarytissueduringtheprocessofinvolutiontheyfoundthatsomemilksecretingepithelialcellschangedintobrown-likeadipocytes,aprocesscalledtransdifferentiation,wherebyacellofonedistincttypeconvertsintoanothertype.Itisstillunclearwhetherthesecellsarebrownorbeigeadipocytes.However,whiteandbeigeadipocytesoriginatefromthesamecellprecursorssuggestingthatthesemammaryadipocytesininvolutingmammarytissuecouldbebeigeadipocytesratherthanbrownadipocytes.Thelactationcyclethereforehighlightsthestrikingfunctionalplasticityofadipocytesinmammarytissue.Theinvestigatorsdidnotcommentonthefunctionsofthebrown-likeadipocytesininvolutingmammarytissue.Clearly,thestudyisanotherexamplehighlightingthemanylivesoffatcellsandtheirunderappreciatedimportanceindiversebiologicalfunctions.
Cinti,S.Theadiposeorganataglance.DisModelMech5,588-594(2012). Giralt,M.&Villarroya,F.White,brown,beige/brite:differentadiposecellsfordifferentfunctions?Endocrinology154,2992-3000(2013). McMillan,A.C.&White,M.D.Inductionofthermogenesisinbrownandbeigeadiposetissues:molecularmarkers,mildcoldexposureandnoveltherapies.Curr
OpinEndocrinolDiabetesObes22,347-352(2015). Kim,S.H.&Plutzky,J.Brownfatandbrowningforthetreatmentofobesityandrelatedmetabolicdisorders.DiabetesMetabJ40,12-21(2016). Giordano,A.etal.Mammaryalveolarepithelialcellsconverttobrownadipocytesinpost-lactatingmice.JCellPhysiolFebruary14edition(2017). Morroni,M.etal.Reversibletransdifferentiationofsecretoryepithelialcellsintoadipocytesinthemammarygland.ProcNatlAcadSciUSA101,16801-16806
(2004).ContributedbyDr.RossTellam(AM)ResearchScientistBrisbane,Australia
EditorialStaffofSPLASH!milkscienceupdate:Dr.DanielleLemay,ExecutiveEditorDr.KatieRodger,ManagingEditorAnnaPetherick,AssociateEditorProf.KatieHinde,ContributingEditorDr.LaurenMilliganNewmark,AssociateEditorDr.RossTellam,AssociateEditorDr.SandeepRavindran,AssociateEditorProf.PeterWilliamson,AssociateEditorCoraMorgan,EditorialAssistantTasslynGester,CopyEditor
FundingprovidedbyCaliforniaDairyResearchFoundationandtheInternationalMilkGenomicsConsortium
TheviewsandopinionsexpressedinthisnewsletterarethoseofthecontributingauthorsandeditorsanddonotnecessarilyrepresenttheviewsoftheiremployersorIMGCsponsors.
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